Interleukiini 13:n vaikutus mikrogliasoluja sisältävien aivokuoriorganoidien lipopolysakkaridin ja interferoni-gamman yhdistelmällä aiheutettuun tulehdustilaan

Neuroinflammation connects various neurodegenerative and neurovascular diseases. Ischemic stroke is one of the leading causes for death and disability. In ischemic stroke, a blood clot blocks brain circulation causing oxygen and nutrient deprivation. Interleukin 13 (IL-13), a natural anti-inflammatory immune signaling molecule previously linked for example to allergic inflammation, has shown to have neuroprotective effects on the outcome of artificially induced ischemic stroke in mice. However, IL-13 appears also detrimental for immune-activated brain-resident immune cells, microglia, specifically found in experiments using rats. Because of differences between species, the results from animal studies do not translate well to humans and many treatments fail in clinical trials. Moreover, the effect of IL-13 on activated human microglia is unknown. Here we show a controlled, artificially induced by lipopolysaccharide (LPS) and interferon-gamma (IFN-γ), neuroinflammation model to test whether IL-13 is toxic or protective for activated human microglia in immunocompetent cortical organoids. Because neuroinflammation is one of the hallmarks of ischemic stroke, the effect of IL-13 on immunocompetent cortical organoids with artificially induced neuroinflammation can be used to predict whether the effect is neuroprotective. LPS/IFN-γ+IL-13-treated immunocompetent cortical organoids showed increased expression for both inflammatory and anti-inflammatory microglia markers. HLA-DRA, a marker for activated microglia, was upregulated in LPS/IFN-γ+IL-13-treated immunocompetent cortical organoids. Also, the general microglial marker IBA1 was upregulated in LPS/IFN-γ+IL-13-treated immunocompetent cortical organoids. No clear difference was observed in the appearance of apoptotic cells between LPS/IFN-γ-treated and LPS/IFN-γ+IL-13-treated immunocompetent cortical organoids. Thus, IL-13 does not appear clearly detrimental for activated human microglia. However, due to limited sample size and high variation between individual organoids, definitive conclusions cannot be drawn. This Master’s thesis project is a pilot study preceding experiments that will use oxygen-glucose deprivation to model ischemic stroke in immunocompetent cortical organoids.